Monday, November 13, 2017

(LML) Steroid Dependency and the use of Methotrexate

Leprosy Mailing List – November 13,  2017

Ref.:   (LML)  Steroid Dependency and the use of Methotrexate

From:  Terence J Ryan, Oxford, UK

Dear Pieter,


Folic acid antagonists (editor: type of drug that stops cells from using folic acid to make DNA and may kill cancer cells - NCI Dictionary of Cancer terms- like for example MTX) have been in use for at least 8 decades. First for Leukaemia and then for Rheumatoid arthritis. It was the subject of the first Medical debate between the UK and USA using Telstar (editor: Telstar is the name of various communications satellites)

-        It was following this, that an Oxford study cautioned about side effects (Ryan et al 1964 British Journal of Dermatology 76 No12 :255-264).

-       After our first death we published further warnings (Ryan et al 1967, British Journal of Dermatology77(letter) page283).

-       With Harvey Baker I did a study of its use in over 100 cases of Generalised Pustular Psoriasis most of to whom it was given after high doses of steroids had suppressed the pituitary.

-       In 1974, I published with Millward Sadler about Methotrexate induced liver disease in Psoriasis (British journal of Dermatology 1974).

-       Harvey Baker and I discussed the prognosis in a paper on Generalised pustular psoriasis in Ryan and Bake r(1971) BJD(1971)85 407-411.

These papers are no longer read because in the UK methotrexate is considered a safe drug once all precautions have been undertaken.

For us beginners folic acid antagonists were a risk in an era of steroid over-usage, drugs like Tetracycline damaging the liver, and inappropriate diets and herbal remedies not yet understood. In the field of Leprosy management they are still a risk and must be used only by those who are fully familiar with the literature.

In as early as 1971, we were as we stated  less  prejudiced against methotrexate than steroids. However, I quote from our 1971 paper:

 "Provided the patient is not debilitated, and methotrexate is well tolerated, such toxicity as occurs is likely to be mild and quickly reversible. In this series methotrexate was certainly responsible for two deaths and partly responsible for four, but these data reflect the dangers of giving the drug to patients who are already desperately ill, who are likely to be on several drugs including steroids and may have a toxic marrow depression or hepatitis."


Today in India especially I would add tuberculosis as a contraindication to steroids but not to methotrexate, but I could be wrong; as was our experience in the days of the use of the Osler Pavilion in Oxford spontaneous remission of diseases was the aim of prolonged admission for several diseases. It is not thought of today.

Our experience at that time was that we believed that we had evidence that steroids prevented improvement in generalised pustular psoriasis (and the process of withdrawal was its principle cause) or erythroderma, until they were withdrawn. As I read my lengthy discussion in the 1964 paper I am impressed by the idea that drugs are of questionable value in some conditions and that the treated group had a more severe disease as a consequence and no or less frequent prolonged remissions. It led to us to stating that:

 "It is probably in the patients interest to stay in hospital for 3 months or even longer, with little active treatment in anticipation of spontaneous remission without treatment".  


It is a sad fact that in the UK we no longer have either the beds or nursing experience for this to be tested. In India I remember at least a few Charitable care homes where the nursing was of a high standard where little active treatment would have been possible.

My experience in the Cochrane Annex at Oxford with my late colleague Colin Macdougall is that several of the cases of ENL he published had either renal or liver problems.

Terence J Ryan

LML - S Deepak, B Naafs, S Noto and P Schreuder

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